Voltage-gated Calcium Channel CaV1.2 functions in non-excitable musculoskeletal tissues
Most studies on CaV1.2 focus on its function in excitable cells such as cardiomyocytes and neurons, where frequent and dynamic changes in membrane potential facilitate activation of this voltage-gated channel. Few studies focused on CaV1.2 in non-excitable cells, which have more restricted changes in membrane potential. Studies of Timothy syndrome (TS), a multiorgan disorder caused by a de novo mutation (G406R) in the CaV1.2 pore forming α1C-encoding CACNA1C gene, however, revealed critical but previously unappreciated roles for CaV1.2 in many non-excitable cells.
The primary interest of the Cao Laboratory is to understand the physiological and pathophysiological contribution of CaV1.2 Ca2+ channel, its activation mechanisms and the molecular basis of Ca2+-dependent cellular processes during non-excitable musculoskeletal tissue (such as bone and tendon) development, postnatal growth and their repair/regeneration upon injury. Our long-term goal aims to translate our findings related to Ca2+ channel and Ca2+ signaling in basic bone and tendon biology to clinical trials in patients to help prevent and treat musculoskeletal diseases such as osteoporosis, tendinopathies, and heterotopic ossification in soft tissues. We utilize genetic mouse models, primary cell culture systems, pharmacological approaches, next-generation sequencing techniques, multiphoton Ca2+ imaging to define the molecular mechanisms and signaling cascades up/downstream of CaV1.2 in bone and tendon formation.